6533b823fe1ef96bd127e260
RESEARCH PRODUCT
The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells
Thorsten KurzAndreas SchlosserMarcus GroettrupThorsten BuchAri WaismanSandra NiendorfWolfgang W. A. SchamelAnja BastersAnnette AichemDeborah YablonskiAnne SchönleAlmut DufnerMarco PrinzKlaus-peter KnobelochAgnes KisserSonja Reissigsubject
Regulatory T cellT-LymphocytesImmunologyReceptors Antigen T-Cell610 Medicine & healthBiologyCD8-Positive T-LymphocytesJurkat cellsJurkat CellsMiceddc:570EndopeptidasesmedicineImmunology and AllergyAnimalsHomeostasisHumans10239 Institute of Laboratory Animal ScienceIL-2 receptorAdaptor Proteins Signal Transducing2403 ImmunologyReceptors Interleukin-7ThymocytesEndosomal Sorting Complexes Required for TransportForkhead Box Protein O1ZAP70T-cell receptorCD28Cell DifferentiationForkhead Transcription FactorsColitisCell biologyThymocytemedicine.anatomical_structure2723 Immunology and Allergy570 Life sciences; biology590 Animals (Zoology)Ubiquitin ThiolesteraseCD8description
The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Rα mediated by the transcription factor Foxo1. Mice with T cell-specific USP8 deficiency developed colitis that was promoted by disturbed T cell homeostasis, a predominance of CD8(+) γδ T cells in the intestine and impaired regulatory T cell function. Collectively, our data reveal an unexpected role for USP8 as an immunomodulatory DUB in T cells.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 |